Bidirectional regulation of kainate receptor surface expression in hippocampal neurons.
Kainate receptors (KARs) are crucial for the regulation of both excitatory and inhibitory neurotransmission, but little is known regarding the mechanisms controlling KAR surface expression. We used super ecliptic pHluorin (SEP)-tagged KAR subunit GluR6a to investigate real-time changes in KAR surface expression in hippocampal neurons. Sindbis virus-expressed SEP-GluR6 subunits efficiently co-assembled with native KAR subunits to form heteromeric receptors. Diffuse surface-expressed dendritic SEP-GluR6 is rapidly internalized following either N-methyl-d-aspartate or kainate application. Sustained kainate or transient N-methyl-d-aspartate application resulted in a slow decrease of base-line surface KAR levels. Surprisingly, however, following the initial loss of surface receptors, a short kainate application caused a long lasting increase in surface-expressed KARs to levels significantly greater than those prior to the agonist challenge. These data suggest that after initial endocytosis, transient agonist activation evokes increased KAR exocytosis and reveal that KAR surface expression is bidirectionally regulated. This process may provide a mechanism for hippocampal neurons to differentially adapt their physiological responses to changes in synaptic activation and extrasynaptic glutamate concentration.
Martin
Stéphane
S
Department of Anatomy, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, United Kingdom.
Bouschet
Tristan
T
Jenkins
Emma L
EL
Nishimune
Atsushi
A
Henley
Jeremy M
JM
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007608:Kainic Acid / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000096:biosynthesis* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012845:Sindbis Virus / Q000378:metabolism; D000097806:GluK2 Kainate Receptor
D018698:Glutamic Acid; D007608:Kainic Acid; D016202:N-Methylaspartate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D000097806:GluK2 Kainate Receptor